Use of visible light spectroscopy to diagnose chronic gastrointestinal ischemia and predict response to treatment.

BACKGROUND & AIMS: Chronic gastrointestinal ischemia (CGI) is more common than previously thought. Visible light spectroscopy (VLS) allows for noninvasive measurements of mucosal capillary hemoglobin oxygen saturation during endoscopy. We evaluated the response of patients with occlusive CGI to treatment after evaluation by radiologic imaging of the vasculature and VLS. We also identified factors associated with response to treatment in these patients. METHODS: In a prospective study, we collected data from 212 patients referred for evaluation of suspected CGI from November 2008 through January 2011. Patients underwent an extensive evaluation that included visualization of gastrointestinal arteries and assessments of mucosal perfusion by means of VLS. Treatment response was evaluated in patients with occlusive CGI. Factors associated with response to therapy were assessed by using multivariate logistic regression analysis. RESULTS: Occlusive CGI was diagnosed in 107 patients (50%); 96 were offered treatment (90%). After median follow-up period of 13 months, data on treatment response were available from 89 patients (93%); 62 patients had a sustained response (70%). Weight loss before treatment (odds ratio [OR], 1.93), presence of an abdominal bruit (OR, 2.36), and corpus mucosal saturation level <56% (OR, 4.84) were the strongest predictors of a positive response to treatment. CONCLUSIONS: Treatment of CGI, diagnosed by a multimodal approach, provides a substantial long-term rate of response (70% in 13 months). Weight loss, abdominal bruit, and low corpus mucosal saturation identify patients most likely to respond to treatment. Multiple techniques should therefore be used to assess patients with CGI, including VLS measurements, to detect mucosal hypoxia.

Radiological imaging and gastrointestinal tonometry add value in diagnosis of chronic gastrointestinal ischemia.

BACKGROUND & AIMS: The diagnosis of chronic gastrointestinal ischemia (CGI) remains a clinical challenge. We aimed to assess the diagnostic value of clinical features, visualization of the gastrointestinal arteries, and evaluation of mucosal perfusion in patients clinically suspected of CGI. METHODS: A total of 186 patients referred for suspicion of CGI were prospectively included and followed up. All patients had an extensive diagnostic work-up, including visualization of the gastrointestinal arteries with computed tomography, magnetic resonance, or conventional angiography, and mucosal perfusion with tonometry. The reference standard for CGI was persistent clinical response after adequate therapy. The diagnostic value of individual and combined tests was assessed with multivariable logistic regression analysis. RESULTS: A total of 116 (62%) patients were diagnosed with CGI. In a multivariable model solely based on clinical features, the strongest predictors for CGI were the presence of postprandial pain, weight loss per month in kilograms, concomitant cardiovascular disease, and presence of an abdominal bruit. However, this model showed limited discriminative ability for the presence or absence of CGI (c-statistic, 0.62). Adding radiologic imaging to the prediction model improved the discriminative ability substantially (c-statistic, 0.81). Adding tonometry to the prediction model further improved the discriminative ability of the model (c-statistic, 0.90). The combination of clinical features and tonometry with a c-statistic of 0.88 approximated the discriminative ability of the latter model. CONCLUSIONS: Clinical features alone have a limited value to assess CGI correctly. Visualization of the gastrointestinal arteries and evaluation of mucosal perfusion substantially improve the diagnosis of CGI. The strongest diagnostic contribution comes from mucosal perfusion assessment.

Endoscopic visible light spectroscopy: a new, minimally invasive technique to diagnose chronic GI ischemia.

BACKGROUND: The diagnosis of chronic GI ischemia (CGI) remains a clinical challenge. Currently, there is no single simple test with high sensitivity available. Visible light spectroscopy (VLS) is a new technique that noninvasively measures mucosal oxygen saturation during endoscopy. OBJECTIVE: To determine the diagnostic accuracy of VLS for the detection of ischemia in a large cohort of patients. DESIGN: Prospective study, with adherence to the Standards for Reporting of Diagnostic Accuracy. SETTING: Tertiary referral center. PATIENTS: Consecutive patients referred for evaluation of possible CGI. INTERVENTIONS: Patients underwent VLS along with the standard workup consisting of evaluation of symptoms, GI tonometry, and abdominal CT or magnetic resonance angiography. MAIN OUTCOME MEASUREMENTS: VLS measurements and the diagnosis of CGI as established with the standard workup. RESULTS: In 16 months, 121 patients were included: 80 in a training data set and 41 patients in a validation data set. CGI was diagnosed in 89 patients (74%). VLS cutoff values were determined based on the diagnosis of CGI and applied in the validation data set, and the results were compared with the criterion standard, resulting in a sensitivity and specificity of VLS of 90% and 60%, respectively. Repeated VLS measurements showed improvement in 80% of CGI patients after successful treatment. LIMITATIONS: Single-center study; only 43% of patients had repeated VLS measurements after treatment. CONCLUSIONS: VLS during upper endoscopy is a promising easy-to-perform and minimally invasive technique to detect mucosal hypoxemia in patients clinically suspected of having CGI, showing excellent correlation with the established ischemia workup.

Hypoxia-inducible factor 1-α in chronic gastrointestinal ischemia.

Chronic gastrointestinal ischemia (CGI) is the result of decreased mucosal perfusion. Typical histological characteristics are lacking which hamper its early diagnosis. Hypoxia-inducible factor-1α (HIF-1α) is expressed under acute hypoxia. We investigated HIF-1α expression in chronic ischemic and inflammatory conditions of the human gastrointestinal (GI) tract. Immunohistochemical expression of HIF-1α was analyzed in 61 patients, including patients with CGI, Helicobacter pylori gastritis, ischemic colitis (IC), infectious colitis, and inflammatory bowel disease (IBD), and 22 controls. HIF-1α expression in >10 % of the cells was regarded as positive staining, and expression <10 % of the cells was considered as negative staining. In the upper GI tract, HIF-1α expression was found in 5/20 CGI patients, but not in controls (p = 0.08). The sensitivity and specificity of HIF-1α expression for diagnosing CGI were 25 and 84%, respectively. In the lower GI tract, HIF-1α was expressed in all patients with IC and infectious colitis and in a majority of IBD patients as well as in 7/12 controls. The sensitivity and specificity of HIF-1α for diagnosing IC were 100 and 51%, respectively. HIF-1α expression was more often (p = 0.02) observed in patients with histological signs of inflammation in the lower GI tract. HIF-1α is expressed in acute and chronic ischemic tissue, but also in normal colon tissue and inflammatory disorders.

Combining radiological imaging and gastrointestinal tonometry: a minimal invasive and useful approach for the workup of chronic gastrointestinal ischemia.

BACKGROUND: The established approach for patients suspected of chronic gastrointestinal ischemia (CGI) includes assessment of medical history, vascular imaging, such as by digital subtraction angiography, and, more recently, computed tomography angiography (CTA) or magnetic resonance angiography. Mucosal perfusion assessment techniques have recently been shown to be of additional diagnostic value, including visible light spectroscopy and gastric exercise tonometry. Gastric exercise tonometry, however, is cumbersome and impossible to perform in a considerable proportion of patients. An alternative approach is provided by 24 h gastrointestinal tonometry (TM). We challenged the use of TM in combination with CTA as an alternative approach to evaluate patients suspected of CGI. METHODS: Patients referred for suspected CGI were prospectively evaluated using CTA and TM, and discussed in a multidisciplinary team, where a consensus diagnosis was made. CGI patients were offered therapy. Persistent symptom relief after adequate therapy during follow-up was used as the 'gold standard' and was defined as a definitive diagnosis of CGI. RESULTS: In 31 months, 186 patients were included (men 69, mean age 63 years). A consensus diagnosis of CGI was made in 128 (69%) patients: 94 with occlusive and 34 with nonocclusive CGI. After a median follow-up of 21 months after a therapeutical intervention, 91% of the CGI patients were free from symptoms. CONCLUSION: In patients clinically suspected of CGI, the combination of CTA and TM provides a minimally invasive, reliable diagnostic approach, which seems to be very useful in clinical practice and to have an outcome similar to the established diagnostic workup.

Patients with chronic gastrointestinal ischemia have a higher cardiovascular disease risk and mortality.

OBJECTIVES: We determined the prevalence of classical risk factors for atherosclerosis and mortality risk in patients with CGI. METHODS: A case-control study was conducted. Patients referred with suspected CGI underwent a standard work-up including risk factors for atherosclerosis, radiological imaging of abdominal vessels and tonometry. Cases were patients with confirmed atherosclerotic CGI. Controls were healthy subjects previously not known with CGI. The mortality risk was calculated as standardized mortality ratio derived from observed mortality, and was estimated with ten-year risk of death using SCORE and PREDICT. RESULTS: Between 2006 and 2009, 195 patients were evaluated for suspected CGI. After a median follow-up of 19 months, atherosclerotic CGI was diagnosed in 68 patients. Controls consisted of 132 subjects. Female gender, diabetes, hypercholesterolemia, a personal and family history of cardiovascular disease (CVD), and current smoking are highly associated with CGI. After adjustment, female gender (OR 2.14 95% CI 1.05-4.36), diabetes (OR 5.59, 95% CI 1.95-16.01), current smoking (OR 5.78, 95% CI 2.27-14.72), and history of CVD (OR 21.61, 95% CI 8.40-55.55) remained significant. CGI patients >55 years had a higher median ten-year risk of death (15% vs. 5%, P = 0.001) compared to controls. During follow-up of 116 person-years, standardized mortality rate was higher in CGI patients (3.55; 95% CI 1.70-6.52). CONCLUSIONS: Patients with atherosclerotic CGI have an increased estimated CVD risk, and severe excess mortality. Secondary cardiovascular prevention therapy should be advocated in patients with CGI.